The affinity shown by 67Ga, 111In, and the higher atomic number rare earth radionuclides for nonosseous tumors in man has provided the basis for a diagnostic test (scanning) for the detection of cancer. Our aim in this project is to determine the cellular binding sites for these radionuclides and to identify the nature of the process(es) and the biochemical agent(s) involved. An understanding of the mechanism(s) involved should lead to methods for enhancement of the affinities of these agents for tumor tissue and also to the identification of other tumor-localizing agents of perhaps even greater tumor specificity. Our goals for the coming year are: (1) We will scale-up our procedure for the separation and purification of a 40,000 (40K) dalton 67Ga-binding glycoprotein that appears to be unique to tumor tissue permitting us to obtain mg quantities of the protein for production of antibody to it. We will in turn then be able to separate 40K glycoprotein and antibody directly from tumor tissue extracts and the serum of immunized rabbits using affinity chromatography techniques; (2) We will complete our characterization of the 40K 67Ga-binding protein and the subcellular microvesicles with which it appears to be associated; (3) We will study the subcellular distribution of 67Ga in the thymus, the organ that we now postulate to be the endogenous source of tumor tissue 40K 67Ga-binding glycoprotein. Nude mice implanted with rat hepatomas will be used to test our hypothesis; and (4) The general nature of the effect of the presence of malignancy on the increased body retention of 67Ga in animals following X-irradiation will be assessed, and, if the effect is found to be general, we will initiate an investigation of the sera of tumor-bearing animals for abnormal 67Ga-binding components.